Contrary to the general contention that inhalation anesthetics act at the liquid part of the cell membrane, we postulate that the site of action of anesthetics in the interfacial region of the cell membrane irrespective of lipid or protein. This project is aimed at demonstrating the perturbing action of inhalation anesthetics upon the surface of lipid-free model proteins. In a protein macromolecule immersed in water, hydrophobic interaction in in competition with ionic bonding, also that the usual ground state in water is for hydrophobic interaction to be present at the expense of the ionic bonds. The resulting exposedcharge attracts water molecules with strong electrostatic force. The attracted water molecules assume a low-volume dense crystalline lattice structure due to the intense physical force. The structure is about 15% more dense than the bulk water. This decrease of the volume is know as electrostriction. The hydrophobic interaction of inhalation anesthetics with proteins would relax their structure and displaces the ionic sites from the interface, and these charges then can neutralize each other. This would decrease the magnitude of electrostriction and the volume of the system increases, and the system becomes susceptible to the high pressure. This change of the state of cluster ofwater molecules structured around the surface charge is the basis for the well-known pressure reversal of anesthesia. The present project is expected to demonstrate the interfacial action of anesthetics upon protein macromolecules and the decrease of the surface charges.